ESKAPE pathogens are considered as global threats to human health. The discovery of new molecules for which these pathogens have not yet developed resistance is a high medical priority. Synthetic flavonoids are good candidates for developing new antimicrobials. Therefore, we report here the potent in vitro antibacterial activity of BrCl-flav, a representative of a new class of synthetic tricyclic flavonoids. Minimum inhibitory/bactericidal concentration, time kill and biofilm formation assays were employed to evaluate the antibacterial potential of BrCl-flav. The mechanism of action was investigated using fluorescence and scanning electron microscopy. A checkerboard assay was used to study the effect of the tested compound in combination with antibiotics. Our results showed that BrCl-flav displayed important inhibitory activity against all tested clinical isolates, with MICs ranging between 0.24 and 125 µg/mL. A total kill effect was recorded after only 1 h of exposing Enterococcus faecium cells to BrCl-flav. Additionally, BrCl-flav displayed important biofilm disruption potential against Acinetobacter baumannii. Those effects were induced by membrane integrity damage. BrCl-flav expressed synergistic activity in combination with penicillin against a MRSA strain. Based on the potent antibacterial activity, low cytotoxicity and pro-inflammatory effect, BrCl-flav has good potential for developing new effective drugs against ESKAPE pathogens.

This study describes the comparison between the interaction of a series of peptide-functionalized chitosan-based nanocapsules and liposomes with two cell lines, i.e., mouse macrophages RAW 264.7 and human endothelial cells EA.hy926. Both types of nanocarriers are loaded with magnetic nanoparticles and designed for anti-inflammatory therapy. The choice of these magnetic nanostructures is argued based on their advantages in terms of size, morphology, chemical composition, and the multiple possibilities of modifying their surface. Moreover, active targeting might be ensured by using an external magnetic field. To explore the impact of chitosan-based nanocapsules and liposomes on cell cytophysiology, the cell viability, using the MTT assay, and cell morphology were investigated. The results revealed low to moderate cytotoxicity of free nanocapsules and significant cytotoxicity induced by chitosan-coated liposomes loaded with dexamethasone, confirming its release from the delivery system. Thus, after 48 h of treatment with nanocapsules, the viability of RAW 264.7 cells varied between 88.18% (OCNPM-1I, 3.125 µg/mL) and 76.37% (OCNPM-1, 25 µg/mL). In the same conditions, EA.hy926 cell viability was between 99.91% (OCNPM-3, 3.125 µg/mL) and 75.15% (OCNPM-3, 25 µg/mL) at the highest dose (25 µg/mL), the values being comparable for both cell lines. Referring to the cell reactivity after dexamethasone-loaded liposome application, the lowest viability of RAW 264.7 cells was 41.25% (CLDM5CP-1, 25 µg/mL) and 58.20% (CLDMM2CP-1 1.25 µg/mL) in the endothelial cell line, proving a selective character of action of nanocarriers. The cell morphology test, performed to support and confirm the results obtained by the MTT test, revealed a differentiated response for the two types of nano-carriers. As expected, an intense cytotoxic effect in the case of dexamethasone-loaded liposomes and a lack of cytotoxicity for drug-free nanocapsules were noticed. Therefore, our study demonstrated the biocompatible feature of the studied nanocarriers, which highlights them for future research as potential drug delivery systems for pharmacological applications, including anti-inflammatory therapy.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is considered the main cause of nosocomial and community-associated infections. Because of antimicrobial resistance, MRSA infections are difficult or impossible to treat, leading to high mortality rates and significant economic and societal costs. In view of the MRSA challenge to public health all over the world, the identification of new and effective anti-MRSA agents is a high medical priority. Objectives: A new series of tricyclic flavonoids with a methyl substituent on ring A of the flavonoid skeleton was synthesized to assess their antimicrobial properties. Methods: The structures of novel synthetic tricyclic flavonoids and their 3-dithiocarbamic flavanones were proven by X-ray structural analyses. Minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) were used to evaluate antimicrobial activity. Growth kinetic and time–kill assays were employed to confirm the antibacterial effectiveness. The mechanism of action was investigated using fluorescence microscopy. Results: Our results show that the tricyclic flavonoids exhibited important antibacterial and antifungal activities, with MIC and MBC values as low as 1.95 µg/mL and 3.90 µg/mL recorded for compound 5e against a multidrug-resistant MRSA strain. Flavonoid 5e induced a more important bacteriostatic effect compared with chloramphenicol, inhibiting the bacterial growth for up to 24 h at concentrations equivalent to 2 × MIC. Also, 5e exhibited a significant bactericidal activity, with no viable cells evidenced after 6 h of incubation in the presence of MBC and a total kill effect recorded up to 24 h. The anti-MRSA activity may be explained by the cell membrane impairment induced by 5e. Conclusions: All the data support the idea that flavonoid 5e is a reliable candidate to develop effective anti-MRSA agents, but further studies are necessary.

The rapid emergence and spread of multidrug-resistant microorganisms is threatening our ability to treat common infections, with serious medical, social, and economic consequences. Despite substantial progress in the global fight against antibiotic resistance, the number of effective antibiotics is rapidly decreasing, underlying the urgent need to develop novel antimicrobials. In the present study, the green synthesis of novel iodine-substituted tricyclic flavonoids has been accomplished using an eco-friendly reagent, HPW-SiO₂, as a cyclization agent for the precursor 3-dithiocarmamic flavanones. In vitro antimicrobial activity of the new compounds was evaluated using minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentrations. All tested compounds displayed potent inhibitory activity against all tested microbial strains, with the lowest MIC values of 0.12 µg/mL and 0.48 µg/mL recorded for compound 5c against Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus. Higher MIC values (7.81 µg/mL) were registered for several flavonoids against Gram-negative bacteria Escherichia coli and Acinetobacter pittii. No inhibitory activity was evidenced against Pseudomonas aeruginosa strain. The highest antifungal activity was displayed by flavonoid 5d against Candida krusei (MIC = 3.9 µg/mL). The same compound also exhibited the most potent bactericidal and fungicidal activity against Bacillus subtilis (0.9 µg/mL) and Staphylococcus aureus (1.97 µg/mL), Candida albicans, and Candida krusei (7.81 µg/mL). Based on the reported results, we believe that the novel iodine-substituted tricyclic flavonoids have good potential to become new antimicrobial agents effective against bacterial and fungal strains, including WHO-priority pathogens.

The environmental impact of petroleum-derived materials has intensified the search for sustainable and biodegradable alternatives consistent with circular economy principles. Mycelium-based composites (MBCs) offer a biological route for transforming low-value lignocellulosic residues into functional materials. This review analyses fungal species, fungal biology, substrates, fabrication strategies, material properties, applications and production costs using the interaction among fungal species, substrate and processing as its organising principle. The literature survey records 126 fungal species tested or screened for composite production. The influence of substrates, cultivation conditions, fabrication methods and post-processing on material properties is critically evaluated. Recent advances in biofabrication and performance improvement are discussed in relation to their technological maturity and cost effectiveness. Applications in packaging, construction, insulation, furniture and textiles, which range from laboratory proofs of concept to commercial products, illustrate the versatility of MBCs, while variability, process standardisation, large-scale manufacturing and performance optimisation remain challenges. The environmental benefits of MBCs are shown to depend more on production steps than on their biological origin alone. The review identifies research priorities for making production more scalable and economically competitive, including species selection, cultivation optimisation and the integration of biological knowledge with material processing. These directions provide a basis for advancing fungal materials within sustainable manufacturing and circular resource use.